Arterial stiffening is the most important cause of increasing systolic and pulse pressure, and for decreasing diastolic pressure beyond 40 years of age. Stiffening affects predominantly the aorta and proximal elastic arteries, and to a lesser degree the peripheral muscular arteries. While conceptually a Windkessel model is the simplest way to visualize the cushioning function of arteries, this is not useful clinically under changing conditions when effects of wave reflection become prominent. Many measures have been applied to quantify stiffness, but all are approximations only, on account of the nonhomogeneous structure of the arterial wall, its variability in different locations, at different levels of distending pressure, and with changes in smooth muscle tone. This article summarizes the methods and indices used to estimate arterial stiffness, and provides values from a survey of the literature, followed by recommendations of an international group of workers in the field who attended the First Consensus Conference on Arterial Stiffness, which was held in Paris during 2000, under the chairmanship of M.E. Safar and E.D. Frohlich.

Background HIV replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers for those with and without HIV infection. Methods For those aged 45–76, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), D-dimer, and cystatin C were compared for 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study with 5,386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). For those aged 33–44, hsCRP and IL-6 were compared for 287 participants in SMART with 3,231 participants in the Coronary Artery Development in Young Adults (CARDIA) Study. Results hsCRP and IL-6 were 55% (p<0.001) and 62% (p<0.001) higher among HIV-infected participants compared to CARDIA. Compared to MESA, hsCRP, IL-6, D-dimer and cystatin C were 50%, 152%, 94%, and 27% higher (p<0.001 for each). For HIV-infected participants on ART with HIV-RNA levels ≤400 copies/mL, levels were higher (p<0.001) than the general population for all biomarkers (by 21% to 60%). Conclusions hsCRP, IL-6, D-dimer and cystatin C are elevated with HIV infection and remain so even after HIV-RNA levels are suppressed with ART. Further research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways in order to guide potential interventions.

BackgroundThe SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors.MethodsA blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated for each quartile (Q) for each biomarker vs the 1st quartile and for 1 SD higher levels. For both treatment groups combined, unadjusted and adjusted HRs were determined using Cox regression models.ResultsThere were 252 participants who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI) for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38, 3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for the DC and VS treatment groups (interaction p-values were >0.30). The addition of the three biomarkers to a model that included baseline covariates significantly improved model fit (p<0.001). Area under the curve (AUC) estimates improved with inclusion of the three biomarkers in a model that included baseline covariates corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p<0.001 for difference).ConclusionsIn HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors. Further research is needed to determine whether these biomarkers can be used to improve CVD risk prediction among HIV positive individuals.

In vivo arterial stiffness is a dynamic property based on vascular function and structure. It is influenced by confounding factors like blood pressure (BP), age, gender, body mass index, heart rate, and treatment. As a consequence, standardization of the measurement conditions is imperative. General and method/device-specific user procedures are discussed. The subject's conditions should be standardized before starting measurements. These conditions include a minimal resting period of 10 min in a quiet room. It also includes prohibitions on smoking, meals, alcohol, and beverages containing caffeine before measurements. The position of the subject and time of measurements should be standardized. In comparative studies, corrections should be made for confounding factors. Repeated measurements are done preferably by the same investigator, and if available validated with user-independent automated procedures. As it is not feasible to discuss all methods or devices measuring arterial stiffness in one article, more attention is given to user procedures of commercially available devices, because these devices are of interest for a wider group of investigators. User procedures of methods/devices are discussed according to the nature of arterial stiffness measured: systemic, regional, or local arterial stiffness. Each section discusses general or method/device-specific user procedures and is followed by recommendations. Each recommendation discussed during the First International Consensus Conference on the Clinical Applications of Arterial Stiffness is quoted with the level of agreement reached during the conference. Also proposals for future research are made.

Background Experimental and physiologic data mechanistically implicate wave reflections in the pathogenesis of left ventricular failure and cardiovascular disease, but their association with these outcomes in the general population is unclear. Objectives To assess the relationship between central pressure profiles and incident cardiovascular events. Methods Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded non-invasively from 5,960 participants in the Multiethnic Study of Atherosclerosis (MESA). The central pressure waveform was separated into forward and reflected waves using a physiologic flow waveform. Reflection magnitude (RM=[reflected/forward wave amplitude] ×100), augmentation index (AIx=[second/first systolic peak] ×100) and pulse pressure amplification (PPA=[radial/aortic pulse pressure] ×100) were assessed as predictors of cardiovascular events (CVE) and congestive heart failure (CHF) during median 7.61 years of follow-up. Results After adjustment for established risk factors, aortic AIx independently predicted hard CVE (HR per 10%-increase=1.08; 95%CI=1.01-1.14; P=0.016), whereas PPA independently predicted all CVE (HR per 10%-increase=0.82; 95%CI=0.70-0.96; P=0.012). RM was independently predictive of all CVE (hazard ratio [HR] per 10%-increase=1.34; 95%CI=1.08-1.67; P=0.009), hard CVE (HR per 10%-increase=1.46; 95%CI=1.12-1.90; P=0.006) and strongly predictive of new-onset CHF (HR per 10%-increase=2.69; 95%CI=1.79-4.04; P<0.0001), comparing favorably to other risk factors for CHF as judged by various measures of model performance, reclassification and discrimination. In a fully-adjusted model, compared to non-hypertensive subjects with low RM, the HR for hypertensive subjects with low RM, non-hypertensive subjects with high RM and hypertensive subjects with high RM were 1.81 (95%CI=0.85-3.86), 2.16 (95%CI=1.07-5.01) and 3.98 (95%CI=1.96-8.05), respectively. Conclusions Arterial wave reflections represent a novel strong risk factor for CHF in the general population.